- Preparation method of diaryl sulfide amine compound
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The invention relates to a preparation method for a diaryl thioether amine compound. Specifically, the invention relates to a preparation method for 1-[2-(2,4-dimethylphenylsulfalkyl)phenyl]piperazine derivative as shown in a formula I which is described in the specification. The preparation method comprises the following steps: subjecting a compound as shown in a formula V and a compound as shown in a formula IV to cyclization, condensation or introduction of an amino protective group; carrying out further condensation; etc. Thus, the target compound is obtained. Compared with other methods, the preparation method provided by the invention has the advantages of good process reproducibility and easy operation and the characteristics of high yield, low cost and high product purity, is more suitable for industrial production and has higher economic benefits.
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Paragraph 0060-0062
(2020/03/12)
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- Design, synthesis, and evaluation of bitopic arylpiperazine-phthalimides as selective dopamine D3 receptor agonists
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The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathways and the sequence similarity between D2R and D3R have rendered the development of D3R-selective ligands challenging. Herein, we designed and synthesized a series of piperazine-phthalimide bitopic ligands based on a fragment-based and molecular docking inspired design. Compound 9i was identified as the most selective D3R ligand among these bitopic ligands. Its selectivity was improved compared to reference compounds 1 and 2 by 9- and 2-fold, respectively, and it was 21-fold more potent than compound 2. Molecular docking demonstrated that the orientation of Leu2.64 and Phe7.39 and the packing at the junction of helices may affect the specificity for D3R over D2R. Functional evaluation revealed that D3R-selective ligand 9i displayed a subpicomolar agonist activity at D3R with a 199-fold increase in potency compared to quinpirole. These results may be useful for the fragment-based design of bitopic compounds as selective D3R ligands.
- Cao, Yongkai,Sun, Ningning,Zhang, Jiumei,Liu, Zhiguo,Tang, Yi-zhe,Wu, Zhengzhi,Kim, Kyeong-Man,Cheon, Seung Hoon
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supporting information
p. 1457 - 1465
(2018/10/02)
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- POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
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Page/Page column 45; 46
(2018/07/29)
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- Design, synthesis and in vitro activity of 1,4-disubstituted piperazines and piperidines as triple reuptake inhibitors
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Monoamine transporters regulate the concentration of monoamine neurotransmitters, which are essential for vital physiological processes, and their dysfunction can cause several central nervous system diseases. Monoamine transporters currently appear to be the potential target in the management of these disorders. In this study, homologation and bioisosterism techniques have been used in the designing of new 1,4-disubstituted piperazines and piperidines. These derivatives were synthesized and evaluated as potential triple reuptake inhibitors for studying the structure-activity relationships. The most advanced compound, 1-(4-(5-benzhydryl-1H-tetrazol-1-yl)butyl)-4-(3-phenylpropyl)piperazine (2i), was able to inhibit monoamine neurotransmitter reuptake in an in vitro test (IC50?=?158.7?nM for 5-HT, 99?nM for NE and 97.5?nM for DA). These novel potent triple reuptake inhibitor-based 1,4-disubstituted piperazine and piperidine scaffolds deserve further systematic optimization and pharmacological evaluation.
- Paudel, Suresh,Acharya, Srijan,Yoon, Goo,Kim, Kyeong-Man,Cheon, Seung Hoon
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p. 2266 - 2276
(2017/03/23)
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- Exploration of substituted arylpiperazine–tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors
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In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine–tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger potency than those with two-carbon and four-carbon linkers. Interestingly, six compounds, 9b, 9c, 9d, 9o, 9q and 9u displayed more effective activity than the standard drug, bupropion. The provided SAR data and potent biological activity can offer useful guidelines for designing dual norepinephrine and dopamine reuptake inhibitors as effective therapeutic agents for treatment of several central nervous system diseases.
- Paudel, Suresh,Acharya, Srijan,Yoon, Goo,Kim, Kyeong-Man,Cheon, Seung Hoon
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p. 5546 - 5555
(2016/10/22)
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- An efficient scale up process for synthesis of N-arylpiperazines
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An efficient protocol for the synthesis of various substituted phenylpiperazines was developed using sulfolane as solvent. The protocol was clean, high yielding and products were obtained in high purities (≥99%). It was also fast and convenient, as the final products were precipitated as hydrochloride salts and could be obtained by filtration. Sulfolane, an aprotic, dipolar, high boiling and recoverable solvent was used as a substitute for common organic solvents.
- Ravilla, Lokesh,Venkata Subba Naidu,Nagarajan, Kuppuswamy
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supporting information
p. 4541 - 4544
(2015/06/30)
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